Scn2a insufficiency alters spontaneous neuronal Ca2+ activity in somatosensory cortex during wakefulness
Summary: SCN2A protein-truncating variants (PTV) can result in neurological disorders such as autism spectrum disorder and intellectual disability, but they are less likely to cause epilepsy in comparison to missense variants. While in vitro studies showed PTV reduce action potential firing, consequ...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223022150 |
| _version_ | 1797657923205201920 |
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| author | Melody Li Mohamed Eltabbal Hoang-Dai Tran Bernd Kuhn |
| author_facet | Melody Li Mohamed Eltabbal Hoang-Dai Tran Bernd Kuhn |
| author_sort | Melody Li |
| collection | DOAJ |
| description | Summary: SCN2A protein-truncating variants (PTV) can result in neurological disorders such as autism spectrum disorder and intellectual disability, but they are less likely to cause epilepsy in comparison to missense variants. While in vitro studies showed PTV reduce action potential firing, consequences at in vivo network level remain elusive. Here, we generated a mouse model of Scn2a insufficiency using antisense oligonucleotides (Scn2a ASO mice), which recapitulated key clinical feature of SCN2A PTV disorders. Simultaneous two-photon Ca2+ imaging and electrocorticography (ECoG) in awake mice showed that spontaneous Ca2+ transients in somatosensory cortical neurons, as well as their pairwise co-activities were generally decreased in Scn2a ASO mice during spontaneous awake state and induced seizure state. The reduction of neuronal activities and paired co-activity are mechanisms associated with motor, social and cognitive deficits observed in our mouse model of severe Scn2a insufficiency, indicating these are likely mechanisms driving SCN2A PTV pathology. |
| first_indexed | 2024-03-11T17:51:32Z |
| format | Article |
| id | doaj.art-fdc80743068a4226a9920660a68ec3ad |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T17:51:32Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-fdc80743068a4226a9920660a68ec3ad2023-10-18T04:31:27ZengElsevieriScience2589-00422023-11-012611108138Scn2a insufficiency alters spontaneous neuronal Ca2+ activity in somatosensory cortex during wakefulnessMelody Li0Mohamed Eltabbal1Hoang-Dai Tran2Bernd Kuhn3Optical Neuroimaging Unit, Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan; Corresponding authorOptical Neuroimaging Unit, Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Okinawa 904-0495, JapanOptical Neuroimaging Unit, Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Okinawa 904-0495, JapanOptical Neuroimaging Unit, Okinawa Institute of Science and Technology Graduate University (OIST), 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan; Corresponding authorSummary: SCN2A protein-truncating variants (PTV) can result in neurological disorders such as autism spectrum disorder and intellectual disability, but they are less likely to cause epilepsy in comparison to missense variants. While in vitro studies showed PTV reduce action potential firing, consequences at in vivo network level remain elusive. Here, we generated a mouse model of Scn2a insufficiency using antisense oligonucleotides (Scn2a ASO mice), which recapitulated key clinical feature of SCN2A PTV disorders. Simultaneous two-photon Ca2+ imaging and electrocorticography (ECoG) in awake mice showed that spontaneous Ca2+ transients in somatosensory cortical neurons, as well as their pairwise co-activities were generally decreased in Scn2a ASO mice during spontaneous awake state and induced seizure state. The reduction of neuronal activities and paired co-activity are mechanisms associated with motor, social and cognitive deficits observed in our mouse model of severe Scn2a insufficiency, indicating these are likely mechanisms driving SCN2A PTV pathology.http://www.sciencedirect.com/science/article/pii/S2589004223022150Molecular neuroscienceCellular neuroscience |
| spellingShingle | Melody Li Mohamed Eltabbal Hoang-Dai Tran Bernd Kuhn Scn2a insufficiency alters spontaneous neuronal Ca2+ activity in somatosensory cortex during wakefulness iScience Molecular neuroscience Cellular neuroscience |
| title | Scn2a insufficiency alters spontaneous neuronal Ca2+ activity in somatosensory cortex during wakefulness |
| title_full | Scn2a insufficiency alters spontaneous neuronal Ca2+ activity in somatosensory cortex during wakefulness |
| title_fullStr | Scn2a insufficiency alters spontaneous neuronal Ca2+ activity in somatosensory cortex during wakefulness |
| title_full_unstemmed | Scn2a insufficiency alters spontaneous neuronal Ca2+ activity in somatosensory cortex during wakefulness |
| title_short | Scn2a insufficiency alters spontaneous neuronal Ca2+ activity in somatosensory cortex during wakefulness |
| title_sort | scn2a insufficiency alters spontaneous neuronal ca2 activity in somatosensory cortex during wakefulness |
| topic | Molecular neuroscience Cellular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223022150 |
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